P864: A PHASE 1 STUDY OF BELANTAMAB MAFODOTIN IN COMBINATION WITH STANDARD OF CARE IN NEWLY DIAGNOSED MULTIPLE MYELOMA: AN INTERIM ANALYSIS OF DREAMM-9
Authors: Saad Z Usmani, Michał Mielnik, Ja Min Byun, Aránzazu Alonso Alonso, Al-Ola Abdallah, Mamta Garg, Hang Quach, Chang-Ki Min, Wojciech Janowski, Enrique Maria Ocio San Miguel, Katja Weisel, Albert Oriol, Irwindeep Sandhu, Paula Rodríguez-Otero, Karthik Ramasamy, Jacqueline Egger, Danaè Williams, Jie MA, Morrys Kaisermann, Marek Hus
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Belantamab mafodotin (belamaf) is a B-cell maturation antigen-binding antibody-drug conjugate that eliminates myeloma cells via direct cell killing and anti-myeloma immune responses. DREAMM-9 (NCT04091126) is an ongoing Phase 1, randomized, dose and schedule evaluation study. Herein, we report updated interim-analysis data. Aims: DREAMM-9 aims to evaluate belamaf plus bortezomib, lenalidomide, and dexamethasone (VRd) in adult patients with transplant-ineligible newly diagnosed multiple myeloma and to establish the recommended dose for future development of belamaf combination therapies in the first-line setting. Methods: Belamaf dose cohorts are shown in the Table. VRd was given every 3 weeks until cycle 8, and Rd every 4 weeks thereafter (Q3/4W). Following safety data from Cohorts 2–5, Cohorts 6–7 were opened in parallel (randomized 1:1) and have shorter follow-up (Table). Safety was the primary endpoint; efficacy and tolerability were secondary endpoints. Minimal residual disease (MRD) was assessed by next-generation sequencing (10-5). Results: As of data cutoff (October 20, 2022), 93 patients were treated across Cohorts 1–7. Median age (range) was 73 (51–88) years, 55% of patients were male, and 84% were white. The most commonly reported non-ocular adverse events (AEs) across all cohorts were thrombocytopenia (46%), constipation (36%), diarrhea (34%), and peripheral sensory neuropathy (31%). Overall, belamaf-related Grade ≥3 AEs occurred in 35% of patients and led to belamaf dose reductions in 7% and dose delays in 63% of all treated patients. Grade ≥3 ocular AEs (keratopathy and visual acuity [KVA] scale) occurred in 53% of all patients and led to dose reductions in 12% and dose delays in 52% of overall patients. Fatal AEs occurred in 7 patients, all unrelated to study treatment. Efficacy results and ocular AEs are summarized in the Table: 100% of patients responded in Cohort 1 (1.9 mg/kg Q3/4W) and Cohort 3 (1.9 mg/kg Q6/8W). Median time to very good partial response or better (≥VGPR) ranged from 2.1 to 3.1 months across cohorts. Highest MRD negativity rates (≥VGPR) were seen in Cohort 1 (83%) and Cohort 3 (67%). Summary/Conclusion: This updated interim analysis demonstrates that belamaf plus VRd has no new safety signals and provides early and deep anti-myeloma responses in patients with transplant-ineligible newly diagnosed multiple myeloma, with high MRD negativity rates. Funding: GSK (Study 209664); drug linker technology licensed from Seagen Inc.; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. This abstract was previously submitted to the American Society of Clinical Oncology (ASCO) Annual Meeting, June 2–6, 2023, and is submitted on behalf of the original authors with their permission. ©2023 American Society of Clinical Oncology, Inc. Reused with permission. All rights reserved. Table. Efficacy and Safety Summary - Cohorts 1 1.9 mg/kg Q3/4W n=12 2 1.4 mg/kg Q6/8W n=12 3 1.9 mg/kg Q6/8W n=12 4 1.0 mg/kg Q3/4W n=15* 5 1.4 mg/kg Q3/4W n=13 6 1.4 mg/kg then 1.0 mg/kg Q9/12W n=14 7 1.9 mg/kg then 1.4 mg/kg Q9/12W n=15* Grade ≥3 ocular AEs (KVA; N=91), % 83 58 92 57 85 7 0 Median follow-up, months 27.6 16.0 16.2 15.3 15.2 2.5 2.0 ORR, % ≥CR VGPR PR MR/SD 100751780 9283808 100831700 80532077 92622380 791421437 53727207 MRD[-], % ≥CR ≥VGPR 7583 3333 5867 3333 4646 714 07 *Safety population n=14. AEs, adverse events; CR, complete response; KVA, keratopathy and visual acuity scale; MR, minor response; MRD, minimal residual disease; ORR, overall response rate; OS, overall survival; PR, partial response; Q, every; SD, stable disease; VGPR, very good partial response; W, weeks. Keywords: Multiple myeloma, Phase I, Minimal residual disease (MRD), B-cell maturation antigen